Biomaterials-Based Technologies in Skeletal Muscle Tissue Engineering.

For many clinically prevalent severe injuries, the inherent regenerative capacity of skeletal muscle remains inadequate. Skeletal muscle tissue engineering (SMTE) seeks to meet this clinical demand. With continuous progress in biomedicine and related technologies including micro/nanotechnology and 3D printing, numerous studies have uncovered various intrinsic mechanisms regulating skeletal muscle regeneration and developed tailored biomaterial systems based on these understandings. Here, the skeletal muscle structure and regeneration process are discussed and the diverse biomaterial systems derived from various technologies are explored in detail. Biomaterials serve not merely as local niches for cell growth, but also as scaffolds endowed with structural or physicochemical properties that provide tissue regenerative cues such as topographical, electrical, and mechanical signals. They can also act as delivery systems for stem cells and bioactive molecules that have been shown as key participants in endogenous repair cascades. To achieve bench-to-bedside translation, the typical effect enabled by biomaterial systems and the potential underlying molecular mechanisms are also summarized. Insights into the roles of biomaterials in SMTE from cellular and molecular perspectives are provided. Finally, perspectives on the advancement of SMTE are provided, for which gene therapy, exosomes, and hybrid biomaterials may hold promise to make important contributions.

A Mesoporous Silica-Loaded Multi-Functional Hydrogel Enhanced Tendon Healing via Immunomodulatory and Pro-Regenerative Effects.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.

Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice.

INTRODUCTION: Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) and its post-translational modifications, especially sumoylation, is crucial in understanding the progression of AD and exploring novel therapeutic avenues. OBJECTIVES: This study investigates the impact of exercise on the sumoylation of IGF1R and its role in ameliorating AD symptoms in APP/PS1 mice, with a specific focus on neuroinflammation and innovative therapeutic strategies. METHODS: APP/PS1 mice were subjected to a regimen of moderate-intensity exercise. The investigation encompassed assessments of cognitive functions, alterations in hippocampal protein expressions, neuroinflammatory markers, and the effects of exercise on IGF1R and SUMO1 nuclear translocation. Additionally, the study evaluated the efficacy of KPT-330, a nuclear export inhibitor, as an alternative to exercise. RESULTS: Exercise notably enhanced cognitive functions in AD mice, possibly through modulations in hippocampal proteins, including Bcl-2 and BACE1. A decrease in neuroinflammatory markers such as IL-1ß, IL-6, and TNF-α was observed, indicative of reduced neuroinflammation. Exercise modulated the nuclear translocation of SUMO1 and IGF1R in the hippocampus, thereby facilitating neuronal regeneration. Mutant IGF1R (MT IGF1R), lacking SUMO1 modification sites, showed reduced SUMOylation, leading to diminished expression of pro-inflammatory cytokines and apoptosis. KPT-330 impeded the formation of the IGF1R/RanBP2/SUMO1 complex, thereby limiting IGF1R nuclear translocation, inflammation, and neuronal apoptosis, while enhancing cognitive functions and neuron proliferation. CONCLUSION: Moderate-intensity exercise effectively mitigates AD symptoms in mice, primarily by diminishing neuroinflammation, through the reduction of IGF1R Sumoylation. KPT-330, as a potential alternative to physical exercise, enhances the neuroprotective role of IGF1R by inhibiting SUMOylation through targeting XPO1, presenting a promising therapeutic strategy for AD.

Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation.

Background: Colorectal cancer (CRC) is the third most prevalent tumor globally. The liver is the most common site for CRC metastasis, and the involvement of the liver is a common cause of death in patients with late-stage CRC. Consequently, mitigating CRC liver metastasis (CRLM) is key to improving CRC prognosis and increasing survival. Exercise has been shown to be an effective method of improving the prognosis of many tumor types. However, the ability of exercise to inhibit CRLM is yet to be thoroughly investigated. Methods: The GSE157600 and GSE97084 datasets were used for analysis. A pan-cancer dataset which was uniformly normalized was downloaded and analyzed from the UCSC database: TCGA, TARGET, GTEx (PANCAN, n = 19,131, G = 60,499). Several advanced bioinformatics analyses were conducted, including single-cell sequencing analysis, correlation algorithm, and prognostic screen. CRC tumor microarray (TMA) as well as cell/animal experiments are used to further validate the results of the analysis. Results: The greatest variability was found in epithelial cells from the tumor group. RPS4X was generally upregulated in all types of CRC, while exercise downregulated RPS4X expression. A lowered expression of RPS4X may prolong tumor survival and reduce CRC metastasis. RPS4X and tumor stemness marker-CD44 were highly positively correlated and knockdown of RPS4X expression reduced tumor stemness both in vitro and in vivo. Conclusion: RPS4X upregulation may enhance CRC stemness and increase the odds of metastasis. Exercise may reduce CRC metastasis through the regulation of RPS4X.

The Revolution of exosomes: From biological functions to therapeutic applications in skeletal muscle diseases.

Skeletal muscle diseases, a broad category encompassing a myriad of afflictions such as acute muscle injury and muscular dystrophies, pose a significant health burden globally. These conditions often lead to muscle weakness, compromised mobility, and a diminished quality of life. In light of this, innovative and effective therapeutic strategies are fervently sought after. Exosomes, naturally extracellular vesicles with a diameter of 30-150 nm, pervade biological fluids. These microscopic entities harbor a host of biological molecules, including proteins, nucleic acids, and lipids, bearing a significant resemblance to their parent cells. The roles they play in the biological theater are manifold, influencing crucial physiological and pathological processes within the organism. In the context of skeletal muscle diseases, their potential extends beyond these roles, as they present a promising therapeutic target and a vehicle for targeted drug delivery. This potentially paves the way for significant clinical applications. This review aims to elucidate the mechanisms underpinning exosome action, their myriad biological functions, and the strides made in exosome research and application. A comprehensive exploration of the part played by exosomes in skeletal muscle repair and regeneration is undertaken. In addition, we delve into the use of exosomes in the therapeutic landscape of skeletal muscle diseases, providing a valuable reference for a deeper understanding of exosome applications in this realm. The concluding section encapsulates the prospective avenues for exosome research and the promising future they hold, underscoring the tremendous potential these diminutive vesicles possess in the field of skeletal muscle diseases. The Translational Potential of this Article. The comprehensive exploration of exosome's diverse biological functions and translational potential in the context of skeletal muscle diseases presented in this review underscores their promising future as a therapeutic target with significant clinical applications, thus paving the way for innovative and effective therapeutic strategies in this realm.

Long head of biceps tendon transposition for massive and irreparable rotator cuff tears: A systematic review and meta-analysis.

BACKGROUND: Superior capsular reconstruction (SCR) with long head of biceps tendon (LHBT) transposition was developed to massive and irreparable rotator cuff tears (MIRCTs); however, the outcomes of this technique remain unclear. AIM: To perform a systematic review of biomechanical outcomes and a meta-analysis of clinical outcomes after LHBT transposition for MIRCTs. METHODS: We performed a systematic electronic database search on PubMed, EMBASE, and Cochrane Library. Studies of SCR with LHBT transposition were included according to the inclusion and exclusion criteria. Biomechanical studies were assessed for main results and conclusions. Included clinical studies were evaluated for quality of methodology. Data including study characteristics, cohort demographics, and outcomes were extracted. A meta-analysis was conducted of the clinical outcomes. RESULTS: According to our inclusion and exclusion criteria, a total of six biomechanical studies were identified and reported an overall improvement in subacromial contact pressures and prevention of superior humeral migration without limiting range of motion (ROM) after LHBT transposition for MIRCTs. A total of five clinical studies were included in the meta-analysis of LHBT transposition outcomes, consisting of 253 patients. The results indicated that compared to other surgical methods for MIRCTs, LHBT transposition had advantages of more significant improvement in ROM (forward flexion mean difference [MD] = 6.54, 95% confidence interval [CI]: 3.07-10.01; external rotation [MD = 5.15, 95%CI: 1.59-8.17]; the acromiohumeral distance [AHD] [MD = 0.90, 95%CI: 0.21-1.59]) and reducing retear rate (odds ratio = 0.27, 95%CI: 0.15-0.48). No significant difference in American Shoulder and Elbow Surgeons score, visual analogue scale score, and University of California at Los Angles score was demonstrated between these two groups for MIRCTs. CONCLUSION: In general, SCR with LHBT transposition was a reliable and economical technique for treating MIRCTs, both in terms of biomechanical and clinical outcomes, with comparable clinical outcomes, improved ROM, AHD, and reduced the retear rates compared to conventional SCR and other established techniques. More high-quality randomized controlled studies on the long-term outcomes of SCR with LHBT transposition are required to further assess.

Progress in studying the impact of hyperlipidemia and statins on rotator cuff injury and repair.

This review delves into the intersection of two prevalent conditions, hyperlipidemia and rotator cuff injuries, both of which bear substantial healthcare burdens. Our investigation begins with an exploration of rotator cuff injuries, common musculoskeletal disorders that severely impair shoulder functionality and quality of life. These injuries are notably pervasive among sports enthusiasts and the older adult, with an incidence rate estimated at 5-10% in the general population. Despite their widespread occurrence and the diverse, multifactorial etiological factors, effective treatment strategies remain elusive. We then examine hyperlipidemia, a metabolic disorder affecting approximately 40% of the global adult population. Characterized by elevated levels of cholesterol and triglycerides, hyperlipidemia can precipitate severe cardiovascular complications and presents a significant socioeconomic burden. Although current management strategies encompass lifestyle modifications and pharmacological interventions, the condition remains a formidable health challenge. Central to this review is the exploration of a potential association between hyperlipidemia and rotator cuff injuries. We aim to synthesize the current understanding of hyperlipidemia's role in the pathophysiology of rotator cuff injuries, thereby offering fresh insights into their common etiological underpinnings, potential therapeutic targets, and drugs, such as Statins. The influence of other lipid-lowering therapeutics on tendon health is also considered, and further research into the molecular pathways and potential therapeutic benefits of these drugs is required. This pursuit aligns with broader efforts to enhance patient outcomes, minimize healthcare burdens, and contribute to the global understanding of these prevalent conditions.

Mechanisms of exercise in the treatment of lung cancer - a mini-review.

Lung cancer constitutes a formidable menace to global health and well-being, as its incidence and mortality rate escalate at an alarming pace. In recent years, research has indicated that exercise has potential roles in both the prevention and treatment of lung cancer. However, the exact mechanism of the coordinating effect of exercise on lung cancer treatment is unclear, limiting the use of exercise in clinical practice. The purpose of this review is to explore the mechanisms through which exercise exerts its anticancer effects against lung cancer. This review will analyze the biological basis of exercise's anticancer effects on lung cancer, with a focus on aspects such as the tumor microenvironment, matrix regulation, apoptosis and angiogenesis. Finally, we will discuss future research directions and potential clinical applications.